An increase in plasma concentration of fibrinogen is associated with a wide variety of inflammatory processes. Indirect evidence of increased fibrinogen synthesis has been found by catabolic turnover studies to occur in inflammation and in patients with intravascular coagulation and reduced plasma fibrinogen concentration. As with other acute phase reactants, the control mechanisms which stimulate increased fibrinogen synthesis are not well delineated. Hormonal stimuli have been demonstrated to be capable of increasing synthesis in large doses, but it is not clear what types of hormonal control occur under physiologic or pathophysiologic circumstances. The possibility that fibrinogen itself or its derivatives (degradation products and fibrin) exert a "feedback" control of fibrinogen synthesis has been examined in the past but with variable results, and often under extreme experimental conditions. Sufficient data exists to indicate such a feedback system probably exists, but its characteristics are unclear. This postulated mechanism is an attractive hypothesis because it would be capable of exerting homeostatic control and would also explain some findings in both clinical and experimental intravascular coagulation. In this study the feedback influence of varying types and sizes of fibrinogen derivatives on fibrinogen synthesis will be studied, using a technique to directly measure synthesis rates. Fibrinogen and fibrin derivatives on fibrinogen synthesis will be studied, using a technique to directly measure synthesis rates. Fibrinogen and fibrin derivatives will be evaluated systematically through use of various forms of purified degradation products. When a purified derivative is identified which has an effect on fibrinogen synthesis, it will be biochemically altered and degraded so as to localize and characterize the active site on the molecule. Interaction of these "feedback" controlling agents with inflammatory and hormonal stimulants of fibrinogen synthesis will be sought. All substances in these studies will be utilized in amounts which might realistically be present in vivo, physiologically or in disease.